Nicotinic acid
|Section2= |Section3= }} Niacin, also known as nicotinic acid and vitamin B3, is the organic compound with the formula HO2CC5H4N. This water-soluble, colourless solid is a derivative of pyridine, featuring a carboxylic acid functional group at the 3-position. The designation vitamin B3 also includes the corresponding amide nicotinamide ("niacinamide"), wherein the CO2H group has been replaced by a CONH2 group. Niacin is a precursor to NADH, NAD, NAD+, and NADP, which play essential metabolic roles in living cells.Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6. Among its many functions, niacin derivatives are involved with detoxification of xenochemicals, DNA repair, and the production of steroid hormones in the adrenal gland. History Niacin was first described by Weidel in 1873 in his studies of nicotine.H. Weidel, "Zur Kenntniss des Nicotins" Justus Liebig's Annalen der Chemie und Pharmacie 1873, volume 165, 330-349. DOI: 10.1002/jlac.18731650212 The original preparation remains useful: the oxidation of nicotine using nitric acid. Niacin was extracted from livers by Conrad Elvehjem who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor."Elvehjem, C. A.; Madden, Robert J.; Strong, F. M.; Woolley, D. W. The isolation and identification of the anti-blacktongue factor. Journal of Biological Chemistry (1938), 123 137-49. When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contains nicotine. The resulting name 'niacin' was derived from "ni"cotinic "ac"id + vitam"in." Niacin is referred to as Vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as "vitamin PP." Dietary needs Severe deficiency of niacin in the diet causes the disease pellagra, whereas mild deficiency slows the metabolism, causing decreased tolerance to cold. Dietary niacin deficiency tends to occur only in areas where people eat corn (maize), the only grain low in niacin, as a staple food, and that do not use lime during meal/flour production. Alkali lime releases the tryptophan from the corn in a process called nixtamalization so that it can be absorbed in the intestine, and converted to niacin.Vitamin B3 University of Maryland Medical Center. The recommended daily allowance of niacin is 2-12 mg/day for children, 14 mg/day for women, 16 mg/day for men, and 18 mg/day for pregnant or breast-feeding women. Pharmacological uses Niacin, when taken in large doses, blocks the breakdown of fats in adipose tissue, thus altering blood lipid levels. Niacin is used in the treatment of hyperlipidemia because it reduces very-low-density lipoprotein (VLDL), a precursor of low-density lipoprotein (LDL) or "bad" cholesterol. Because niacin blocks breakdown of fats, it causes a decrease in free fatty acids in the blood and, as a consequence, decreased secretion of VLDL and cholesterol by the liver.T. Katzung, Basic and Clinical Pharmacology, 9th ed. p. 570. By lowering VLDL levels, niacin also increases the level of high-density lipoprotein (HDL) or "good" cholesterol in blood, and therefore it is sometimes prescribed for patients with low HDL, who are also at high risk of a heart attack.Postgraduate MedicineCanner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245-1255. An extended release formulation of niacin for this indication is marketed by Abbott Laboratories under the trade name Niaspan by prescription in the United States; Slo-Niacin, made by Upsher-Smith Laboratories, is available over the counter. Niacin is sometimes consumed in large quantities by people who wish to fool drug screening tests, particularly for lipid soluble drugs such as marijuana.Niacin abuse in the attempt to alter urine drug tests. Toxicity People taking pharmacological doses of niacin (1.5 - 6 g per day) often experience a syndrome of side-effects that can include one or more of the following:J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.991. * dermatological complaints **facial flushing and itching **dry skin **skin rashes including acanthosis nigricans * gastrointestinal complaints **dyspepsia (indigestion) * liver toxicity **fulminant hepatic failure * hyperglycemia * cardiac arrhythmias * birth defects Facial flushing is the most commonly-reported side-effect.NIH Medline Plus: Niacin. http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm. It lasts for about 15 to 30 minutes, and is sometimes accompanied by a prickly or itching sensation. This effect is mediated by prostaglandins and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. Taking the niacin with meals also helps reduce this side-effect. After 1 to 2 weeks of a stable dose, most patients no longer flush. Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects.J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.991.T. Katzung, Basic and Clinical Pharmacology, 9th ed. p. 570.Options for therapeutic intervention: How effective are the different agents? European Heart Journal Supplements Vol 8 Suppl F Pp. F47-F53 http://eurheartjsupp.oxfordjournals.org/cgi/content/abstract/8/suppl_F/F47 One study showed the incidence of flushing was 4.5x lower (1.9 vs. 8.6 episodes in the first month) with a sustained-release formulation.Chapman M, Assmann G, Fruchart J, Sheperd J, Sirtori C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid - a position paper developed by the European Consensus Panel on HDL-C. Cur Med Res Opin. 2004 Aug;20(8):1253-68. Doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.992. High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus.J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.991. Hyperuricemia is another side-effect of taking high-dose niacin; thus niacin may worsen gout . Niacin at doses used in lowering cholesterol has been associated with birth defects in laboratory animals and should not be taken by pregnant women.J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.992. Niacin at extremely high doses can have life-threatening acute toxic reactions. One patient suffered vomiting after taking eleven 500-milligram niacin tablets over 36 hours, and another was unresponsive for several minutes after taking five 500-milligram tablets over two days.Hazards: Niacin to Pass a Drug Test Can Have Dangerous Results, By ERIC NAGOURNEY, New York Times, April 17, 2007http://www.nytimes.com/2007/04/17/health/17haza.htmlMittal MK, Florin T, Perrone J, Delgado JH, Osterhoudt KC. Toxicity From the Use of Niacin to Beat Urine Drug Screening. Ann Emerg Med. 2007 April 4. http://www.annemergmed.com/article/PIIS0196064407000741/abstract Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness.JD Gass, Nictonic Acid Maculopathy, Am. J. Opthamology, 1973;76:500-10 Inositol hexanicotinate One popular form of dietary supplement is inositol hexanicotinate, usually sold as "flush-free" or "no-flush" niacin (although those terms are also used for regular sustained-release.) While this form of niacin does not cause the flushing associated with the nicotinic acid form, it is not clear whether it is pharmacologically equivalent in its positive effect.No-Flush Niacin for the Treatment of Hyperlipidemia Biosynthesis The liver can synthesize niacin from the essential amino acid tryptophan (see below), but the synthesis is extremely inefficient; 60 mg of tryptophan are required to make one milligram of niacin.Oxidization Reactions of Niacin from the Linus Pauling Institute at Oregon State University Linus Pauling Institute. The 5-membered aromatic heterocycle of the essential amino acid, tryptophan, is cleaved and rearranged with the alpha amino group of tryptophan into the 6-membered aromatic heterocycle of niacin by the following reaction: : → kynurenine → niacin]] Receptor The receptor for niacin is a G-protein coupled receptor called HM74A.medscape.com - The Metabolic Syndrome: Etiology, Controversies, and Emerging ... It couples to Gi.Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors Christian Zellner 1 *, Clive R. Pullinger 1, Bradley E. Aouizerat 2, Philip H. Frost 1, Pui-Yan Kwok 1, Mary J. Malloy 1, John P. Kane Food sources See also *Nicotinamide *Schizophrenia - Adrenochrome hypothesis mega doses may treat schizophrenia? References External links Category:Acids Category:Hypolipidemic agents Category:B vitamins Category:Vasodilator drugs